^18F—Fallypride标记前体的反相HPLC测定

^18F-Fallypride化学名为（s）-（-）-N-（1-烯丙基吡咯烷-2-氨基甲基）-5-氟[墙F]-2，3-二甲氧基苯甲酰胺（结构式见图1），是一种安全有效的新型多巴胺D2受体PET显像剂，与脑内D2受体具有高亲和力和适宜的亲脂性，且所携带的正电子核素坞F半衰期短（约110min），对人体安全无毒。利用该显像剂结合PET（正电子发射计算机断层显像）、micrOPET（小动物专用正电子发射计算机断层显像）等可活体、无创、     

自动化制备多巴胺转运蛋白显像剂11C-β-CFT及其在正常新生猪脑内PET/CT显像中的应用

目的 在线自动化制备多巴胺转运蛋白显像剂11C-甲基-N-2β-甲基酯-3β-(4-氟-苯基)托烷(11C-β-CFT),并用以进行新生猪PET/CT脑显像.方法 使用GE Tracerlab Fx-pro合成模块自动合成11C-β-CFT.对3只正常新生猪进行11C-β-CFT PET/CT 3D动态显像,观察脑内基底节放射性随时间的变化,并绘制时间-活性曲线.结果 在线自动化制备的11C-β-CFT放射化学纯度>98%,比活度>370 MBq/μmol,最终获得11C-β-CFT 20 mCi.PET/CT 3D脑动态显像显示,静脉注射后5 min内即可见11C-β-CFT在大脑皮质、小脑及基底节区域放射性分布较高,脑白质放射性分布较低,左右侧放射性浓聚程度对称;随着时间延长,大脑皮质、小脑的放射性明显减低,而基底节显示清晰.结论 在线自动化制备11C-β-CFT简单方便、速度快、放化纯度高,可用于进行新生猪的脑受体方面的研究.     

~(18)F-Fallypride标记前体的反相HPLC测定

18F-Fallypride化学名为(s)-(-)-N-(1-烯丙基吡咯烷-2-氨基甲基)-5-氟[18F]-2, 3-二甲氧基苯甲酰胺(结构式见图1), 是一种安全有效的新型多巴胺D2 受体PET显像剂[1], 与脑内D2受体具有高亲和力和适宜的亲脂性,且所携带的正电子核素18F半衰期短(约110 min), 对人体安全无毒.利用该显像剂结合PET(正电子发射计算机断层显像)、microPET(小动物专用正电子发射计算机断层显像)等可活体、无创、动态地显像以观察脑内多巴胺D2受体变化,为脑神经疾病研究提供了新型的有效手段,为精神分裂症、癫痫、兴奋剂成瘾等的发病机制及防治研究提供了真实、客观的依据[2-5].本实验室在国内首次制备了18F-Fallypride的标记前体,化学名为(s)-(-)-N-(1-烯丙基吡咯烷基-2-氨基甲基)-5-(3-苯-磺酰氧丙基)- 2, 3-二甲氧基苯甲胺(结构式见图2), 可方便临床医师制备18F-Fallypride, 用于多种D2受体相关疾病的即时、早期诊断.18F-Fallypride标记前体的质量控制对于提高18F-Fallypride的合成效率和放射化学纯度、保证18F-Fallypride的显像质量是非常重要的.作者利用高效液相色谱法(HPLC)高效、高灵敏度的分离特点,建立了反相HPLC测定标记前体含量的方法,简便可靠,为标记前体的质控提供了有效手段.现报告如下.     

18F-FDG PET/CT鉴别诊断椎骨良恶性病变的临床价值

随着正电子显像设备,包括带符合线路的单光子发射计算机体层摄影仪(MCD-SPECT)、正电子发射计算机体层摄影仪(PET)以及MCD-SPECT/CT和PET/CT,在国内的推广使用,正电子显像在诊断和鉴别诊断骨骼疾病的应用也越来越广泛。其中,PET/CT作为当今正电子显像的尖端设备,在鉴别椎体良恶性病变的临床应用中,逐渐显示出其独特的优势。目前,用于鉴别诊断椎体良恶性病变的正电子显像中,最常用的是~(18)F-氟脱氧葡萄糖(~(18)F-FDG)代谢显像和18F骨显像。~(18)F-FDG是正电子设备单位的常规显像剂,这与其临床适应证范围广、药物供应相对充…     

肿瘤患者示踪剂~(18)F-FDG注射中的护理体会

正PET-CT是将正电子发射计算机断层显像(PET)和电子计算机X射线断层扫描技术(CT)结合在一起,从而反映病变基因、分子、代谢、功能状态和实现对患者体层检查显像检查系统[1]。氟代脱氧葡萄糖(~(18)F-FDG)为葡萄糖类似物,在PET-CT检查中能够通过病灶对显像剂的摄取准     

18F-氟代脱氧葡萄糖PET/CT在乳腺癌诊疗中的应用

正电子发射断层显像(PET)是利用正电子放射性示踪剂显示活体组织器官内生化状态的显像技术.18F-氟代脱氧葡萄糖(18F-FDG )是目前应用最成熟的放射性示踪剂.PET与计算机辅助断层摄影(CT)同机融合技术(PET/CT)实现了PET与CT技术的优势互补本文重点介绍18F-FDG PET/CT显像原理、在乳腺癌诊断中的应用及早期监测化疗疗效.     

1例重度敌敌畏中毒致心跳呼吸骤停的急救护理体会

<正>敌敌畏,又名DDVP,化学名O,O-二甲基-O-(2,2-二氯乙烯基)磷酸酯,是我国农村地区常用的一种有机磷杀虫剂,毒性强。在体内与胆碱酯酶形成磷酰化胆碱酯酶,胆碱酯酶活性受抑制,不能分解乙酰胆碱,致组织中乙酰胆碱过量蓄积,使胆碱能神经过度兴奋,引起毒蕈碱样、烟碱样和中枢神经系统症状,严重者并发呼吸衰竭、脑水肿,甚至死亡,病死率达10%~20%~([1-5])。     

99mTcO（DGDTC）2肺腺癌Spca-1荷瘤裸鼠实验研究

目的用99mTcO核标记D-葡萄糖氨基酸盐配合物99mTcO(DGDTC)2观察其在肺腺癌(Spca-1)荷瘤裸鼠体内的摄取情况,并与18F-2-氟-2-脱氧-D-葡萄糖(18F-FDG)的分布情况进行比较,分析99mTcO(DGDTC)2作为肿瘤代谢显像剂的可行性。方法配体交换法制备99mTcO(DGDTC)2,将Spca-1荷瘤裸鼠模型50只分为99mTcO(DGDTC)2组和18F-FDG组,检测血液、肝、肾、肌肉、肿瘤中的单位放射性计数比值(%ID/g)及肿瘤与非肿瘤(T/NT)放射性比值。结果高效液相层析(HPLC)分析法测定99mTcO(DGDTC)2放射性化学纯度≥95%。荷瘤裸鼠体内分布实验结果显示,99mTcO(DGDTC)2组注射显像剂后30 min时血液、肾内%ID/g最高,1 h时显著降低。注射显像剂后30 min、1 h、2 h、3h和4 h时肿瘤组织的%ID/g分别为5.16±0.96、3.18±0.73、1.94±0.39、0.86±0.15和0.34±0.09;T/NT分别为1.7、3.2、3.8、1.9和1.4。18F-FDG组注射显像剂后10 min时血液、肾内%ID/g最高,以后逐渐下降,肿瘤%ID/g最高值出现在10min时。T/NT比值在60 min时达最高值2.5,以后逐渐下降。结论 99mTcO(DGDTC)2放射稳定性较好,荷瘤裸鼠体内分布显示具有较好的肿瘤靶向性,类似于18F-FDG,是一种很有发展前景的肿瘤代谢显像剂。     

18F-FDG PET在结直肠癌诊断、治疗及预后评价中的作用

正电子发射断层显像(PET)是一种能够识别肿瘤内生理、生化变化的功能性影像诊断技术.在过去十余年中,随着[(18)氟]-2-脱氧葡萄糖正电子发射断层显像(18F-FDG PET)在临床实践中的不断推广和应用,18F-FDG PET对肿瘤的分期、分型,复发、转移的早期诊断,坏死与存活组织的鉴别,肿瘤生物特征的预测及治疗反应的监测作用都得到了广泛承认,在临床肿瘤学中发挥越来越重要的作用[1～3].     

消化系统肿瘤病人18 F-氟代脱氧葡萄糖PE T/C T显像检查中的护理效果观察

[目的]观察消化系统肿瘤病人~(18)F-氟代脱氧葡萄糖(~(18)F-FDG)正电子发射计算机断层显像(PET)/CT显像检查中的护理效果。[方法]选择62例于2018年1月—2018年10月入住医院的消化系统肿瘤病人,在其空腹状态下进行~(18)F-FDG静脉注射后嘱其静卧于床上休息,并于60 min后行PET/CT检查。[结果]1次显像顺利完成检查的共有59例病人,另外3例病人初次显像图像与诊断要求不相符,对其进行护理后再次显像,图像质量达到了相应的要求。[结论]在消化系统肿瘤病人~(18)F-FDG PET/CT显像检查中给予积极有效的护理可确保病人~(18)F-FDG PET/CT显像图像质量。     

Feasibility of 2–deoxy–2–[18F]fluoro–D–glucose– A85380–PET for imaging of human cardiac nicotinic acetylcholine receptors in vivo

Summary  Nicotinic acetylcholine receptors mediate the parasympathetic autonomic control of cardiac function. Aim of this study was the assessment of cardiac nicotinic acetylcholine receptor distribution with a novel (α₄β₂) nicotinic acetylcholine receptor PET ligand (2–deoxy–2– [¹⁸F]fluoro–D–glucose–A85380) in humans. Five healthy volunteers without cardiac disease and six patients with either Parkinson's disease or multiple system atrophy without additional overt cardiac disease were evaluated with 2–deoxy–2–[¹⁸F]fluoro–D–glucose–A85380 PET–imaging to assess the cardiac parasympathetic innervation and the putative impact of both disorders. 2–deoxy–2– [¹⁸F]fluoro–D–glucose–A85380 whole body PET–scans were performed on a Siemens PET/CT biograph^TM 75.4 min±6.7 after i.v. injection of 371.2±58.1 MBq. Average count rate density of left ventricle ROI's and a standard ROI in the right lung were measured within three consecutive slices of 10.0 mm thickness. Heart–to–lung ratios were calculated in each volunteer and patient. Tracer uptake in the left ventricle could be measured in all of the five volunteers and the six patients. Heart–to–lung ratios in the volunteer group were not different from patients suffering from Parkinson's disease or MSA (3.2 ± 0.5 vs 3.2 ± 0.8 and 2.96±0.7, mean ± SD), respectively. Human cardiac nicotinic acetylcholine receptors can be visualized and measured by 2–deoxy–2– [¹⁸F]fluoro–D–glucose–A85380 PET scans both in cardiac–healthy subjects and patients suffering from Parkinson's disease or multiple system atrophy. The heart– as well as the lung–tracer uptake was almost constant throughout all subjects leading to a good target–to–background ratio. These first results suggest no impact of either PD or MSA on cardiac nicotinic acetylcholine receptors. The Article “Feasibility of 2-deoxy-2-[¹⁸F]fluoro-D-glucose-A85380-PET for imaging of human cardiac nicotinic acetylcholine receptors in vivo” by J. Bucerius et al. (the online version can be found at has been published in issue 95 (2006):105–109. Unfortunately a wrong notation for the tracer was given. Instead of 2-deoxy-2-[¹⁸F]fluoro-D-glucose-A85380 it should be 2-[¹⁸F]-A85380. The publisher apologies for any inconvenience caused by this mistake.     

Evaluation of drug penetration into the brain: a double study by in vivo imaging with positron emission tomography and using an in vitro model of the human blood-brain barrier

The blood-brain barrier (BBB) permeabilities of 11 compounds were measured both in vitro with a newly developed coculture-based model of human BBB and in vivo with positron emission tomography (PET). The 11 compounds were fluoropyridinyl derivatives labeled with the positron-emitter fluorine-18, [(18)F]F-A-85380 [2-[(18)F]fluoro-3-[2(S)-2 azetidinylmethoxy]pyridine], and 10 selected N-substituted-azetidinyl and pyrrolidinyl closely related [(18)F]fluoropyridinyl derivatives (including [N'-aromatic/aliphatic]-thioureas, -ureas, and -amides). The in vitro BBB model, a new coculture system of primary human brain endothelial cells and astrocytes, was used to measure the permeability coefficient for each compound. Dynamic PET studies were performed in rats with the same compounds, and a two-compartment model analysis was used to calculate their in vivo permeability coefficients. The 11 derivatives differed in their degree of BBB passage and transport mechanism. The analysis of PET data showed a significant cerebral uptake for six derivatives, for which the in vitro evaluation indicated active influx or free diffusion. Five derivatives displayed low in vivo cerebral uptake, in agreement with the observation of an in vitro active efflux. Overall, there was a remarkable correlation between the in vitro and in vivo permeability coefficients (r = 0.99). This double study proves a close correlationship between the assessment of the BBB passage in vitro and in vivo. The in vitro model of human BBB offers the possibility of subtle discrimination of various BBB permeability degrees and transport mechanisms. Conversely, small animal PET imaging appears suitable to screen directly in vivo brain targeting of drugs or radiopharmaceutical candidates.     

Pharmacological and toxicological evaluation of 2-fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-F-A-85380), a ligand for imaging cerebral nicotinic acetylcholine receptors with positron emission tomography

2-[(18)F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[(18)F]F-A-85380), a positron emission tomography (PET) radioligand for neuronal alpha4beta2(*) nicotinic acetylcholine receptors, was evaluated for its pharmacology and safety. In the Ames test for mutagenicity, 2-F-A-85380 was without effect in five bacterial strains. No evidence of gross pathology or histopathological changes occurred in either 2-day acute (0.4-4000 nmol/kg i.v.) or 14-day expanded acute (40-4000 nmol/kg i.v.) toxicity studies in mice. Similarly, hematology and serum chemistry values in rhesus monkeys administered 60 nmol/kg i.v. were not affected over 14 days. Like nicotine, 2-F-A-85380 produced convulsions in mice at very high doses. The ED(50) value of 2-F-A-85380 for eliciting tonic-clonic convulsions (5.0 micromol/kg i.v.) was nearly 4 times greater than that of nicotine (ED(50) = 1.4 micromol/kg i.v.). Lower doses of 2-F-A-85380 (30-300 nmol/kg i.v.) and nicotine (20-400 nmol/kg i.v.) increased systolic and diastolic blood pressure, heart rate, and cardiac contractility in rats. Notably, the PR, QRS, or QTc intervals of the rat electrocardiogram were unaffected by either drug. Dosimetry studies indicated that the urinary bladder wall was the critical organ and total radiation exposure was within acceptable limits. Estimated doses of 2-F-A-85380 required to elevate blood pressure and heart rate by 10% ranged from 40 to 58 nmol/kg i.v. Nevertheless, the estimated radiopharmaceutically relevant dose of [(18)F]2-F-A-8380 required for initial PET imaging studies, 10 pmol/kg, is less than 1/4000th of the doses calculated (40-58 nmol/kg i.v.) to elevate blood pressure and heart rate by 10% in humans and should elicit no clinically significant effects and have acceptable dosimetry.     

Preclinical In Vitro and In Vivo Characterization of Synaptic Vesicle 2A–Targeting Compounds Amenable to F-18 Labeling as Potential PET Radioligands for Imaging of Synapse Integrity

Molecular Imaging and Biology - Current synaptic vesicle 2A (SV2A) positron emission tomography (PET) imaging agents include the nanomolar affinity probes [11C]UCB-J and [18F]UCB-H derived from the...     

Nicotinic alpha4beta2 receptor binding in dementia with Lewy bodies using 123I-5IA-85380 SPECT demonstrates a link between occipital changes and visual hallucinations

INTRODUCTION: To investigate in vivo differences in the distribution of alpha4beta2 subtypes of nAChR using the ligand (123)I-5-Iodo-3-[2(S)-2-azetidinylmethoxy] pyridine (5IA-85380) and single photon emission computed tomography (SPECT) in DLB and similarly aged controls. METHODS: Thirty-one subjects (15 DLB and 16 controls) underwent (123)I-5IA-85380 and perfusion ((99m)Tc-exametazime) SPECT scanning. Patient scans were compared to scans of control subjects on a voxel-by-voxel basis using SPM2. RESULTS: Compared to controls, significant reductions in relative (123)I-5IA-85380 uptake were identified in frontal, striatal, temporal and cingulate regions in DLB. Elevation of scaled (123)I-5IA-85380 uptake in occipital cortex was observed in DLB relative to controls, as well as being associated with DLB subjects with a recent history of visual hallucinations. Changes in (123)I-5IA-85380 SPECT in DLB were different from perfusion. CONCLUSION: Reductions in normalised (123)I-5IA-85380 uptake in DLB were distinct from their perfusion deficits. Significant increase in occipital lobe uptake was present in DLB, a change most pronounced in subjects with a recent history of visual hallucinations. The findings directly link cholinergic changes in occipital lobe to visual hallucinations in DLB.     

Declines in different beta2* nicotinic receptor populations in monkey striatum after nigrostriatal damage

In the present study we used the nicotinic ligand 5-iodo-A-85380 [5-iodo-3(2(S)-azetidinylmethoxy)pyridine], which selectively binds to beta2-containing nicotinic acetylcholine receptors, to elucidate the nicotinic receptor subtypes affected by nigrostriatal damage in the monkey. Autoradiographic studies in control monkeys showed that 5-[(125)I]A-85380 ([(125)I]A-85380) binds throughout the brain with the characteristics of a nicotinic receptor ligand. Competition experiments with cytisine and nicotine yielded K(i) values of approximately 1 and 10 nM, respectively, with complete inhibition of [(125)I]A-85380 binding at a 10(-6) M concentration of these ligands. In contrast, alpha-conotoxin MII blocked radioligand binding in the striatum by 30% at the highest concentrations, suggesting that a subset of striatal [(125)I]A-85380 sites are alpha-conotoxin MII-sensitive. Monkeys treated with the nigrostriatal neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine showed a selective decrease in striatal [(125)I]A-85380 sites, with a 42% reduction in the caudate and putamen of animals with moderate nigrostriatal lesioning and a 53% decline in the striatum of severely lesioned animals. Our previous work had demonstrated that there were two populations of nicotinic receptors eliminated after nigrostriatal damage, an alpha-conotoxin MII-sensitive and an alpha-conotoxin MII- resistant subtype. Analysis of both striatal [(125)I]A-85380 and [(125)I]epibatidine competition studies extend our earlier studies by demonstrating that the alpha-conotoxin MII-sensitive sites eliminated after moderate nigrostriatal lesioning appear to be composed of two nicotinic receptor subtypes. The data may be important for potential therapeutic approaches because they suggest that there are at least three populations of nicotinic receptors in monkey striatum, of which two are selectively vulnerable to nigrostriatal damage, while the third is more resistant.     

Feasibility of 2–deoxy–2–[18F]fluoro–D–glucose– A85380–PET for imaging of human cardiac nicotinic acetylcholine receptors in vivo

Summary Nicotinic acetylcholine receptors mediate the parasympathetic autonomic control of cardiac function. Aim of this study was the assessment of cardiac nicotinic acetylcholine receptor distribution with a novel (α₄β₂) nicotinic acetylcholine receptor PET ligand (2–deoxy–2– [¹⁸F]fluoro–D–glucose–A85380) in humans. Five healthy volunteers without cardiac disease and six patients with either Parkinson's disease or multiple system atrophy without additional overt cardiac disease were evaluated with 2–deoxy–2–[¹⁸F]fluoro–D–glucose–A85380 PET–imaging to assess the cardiac parasympathetic innervation and the putative impact of both disorders. 2–deoxy–2– [¹⁸F]fluoro–D–glucose–A85380 whole body PET–scans were performed on a Siemens PET/CT biograph^TM 75.4 min±6.7 after i.v. injection of 371.2±58.1 MBq. Average count rate density of left ventricle ROI's and a standard ROI in the right lung were measured within three consecutive slices of 10.0 mm thickness. Heart–to–lung ratios were calculated in each volunteer and patient. Tracer uptake in the left ventricle could be measured in all of the five volunteers and the six patients. Heart–to–lung ratios in the volunteer group were not different from patients suffering from Parkinson's disease or MSA (3.2 ± 0.5 vs 3.2 ± 0.8 and 2.96±0.7, mean ± SD), respectively. Human cardiac nicotinic acetylcholine receptors can be visualized and measured by 2–deoxy–2– [¹⁸F]fluoro–D–glucose–A85380 PET scans both in cardiac–healthy subjects and patients suffering from Parkinson's disease or multiple system atrophy. The heart– as well as the lung–tracer uptake was almost constant throughout all subjects leading to a good targetto– background ratio. These first results suggest no impact of either PD or MSA on cardiac nicotinic acetylcholine receptors. An erratum to this article is available at .     

Preparation,in vitro and in vivo evaluation,and molecular dynamics (MD) simulation studies of novel F-18 labeled tumor imaging agents targeting focal adhesion kinase (FAK)

Focal adhesion kinase (FAK) has been identified as a promising target in the early diagnosis and therapy of tumor. In this work, we obtained and evaluated another two novel pyrimidine-based F-18 labeled tumor imaging agents targeting FAK. Among them, the corresponding F-19 standards [¹⁹F]2, displayed inhibition of FAK with IC₅₀ values of 57.1 nM (better than the results in our published work) and showed an good selectivity profile against some other kinds of cancer-related kinases. [¹⁸F]2 also had relatively good results in the in vivo biodistribution in S180-tumor-bearing mice, with tumor uptake of 5.40 ± 0.12 and 5.96 ± 0.09 % ID per g at 15 and 30 min post-injection, respectively. What''s more, [¹⁸F]2 could be accumulated in tumor at 30 min post-injection, which could be observed from the coronal micro-PET images of mice bearing S180 tumor. In addition, the blocking study for the [¹⁸F]2 with PF-562271 (one of the well-known best selective FAK inhibitor), displayed distinct reduction in the uptake of the radiotracer in tumor at 30 min post-injection in mice, suggesting that the uptake of [¹⁸F]2 in tumor was due to FAK over-expression or high expression in tumor. And the results of the molecular dynamics (MD) simulations and the docking studies were in consistent with the changing trends of the interaction between the F-19 standards and the FAK. Finally, in order to further increase the uptake of the F-18 labeled tracer in tumor, the following points should arouse attention, which could also be considered as the new findings and contributions of this study to the field of the tumor imaging agents: (1) the F-18 labeled tumor radiotracers which have closer interaction with the FAK, should be further designed, via building of models such as 3D-QSAR model to make reasonable guidance to our drug design and consideration of some functional groups which have hydrogen-bonding or salt-bridge interactions with key residues in the kinase domain of FAK; (2) the F-18 radiotracers with better pharmacokinetic properties should be designed, via building of dynamic drug absorption and distribution model in different tissues, to predict whether the molecules have ideal absorption in tumor and low uptake in non-target tissues. The relevant study is being undertaken.

Coronal micro-PET images of mice bearing S180 tumor at 30 min post-injection of [¹⁸F]2.     

[11C]-DPA-713 and [18F]-DPA-714 as New PET Tracers for TSPO: A Comparison with [11C]-(R)-PK11195 in a Rat Model of Herpes Encephalitis

Background  

Activation of microglia cells plays an important role in neurological diseases. Positron emission tomography (PET) with [¹¹C]-(R)-PK11195 has already been used to visualize activated microglia cells in neurological diseases. However, [¹¹C]-(R)-PK11195 may not possess the required sensitivity to visualize mild neuroinflammation. In this study, we evaluated the PET tracers [¹¹C]-DPA-713 and [¹⁸F]-DPA-714 as agents for imaging of activated microglia in a rat model of herpes encephalitis.